Abstract
Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single-target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients.
Keywords: Polypharmacology, systems pharmacology, off-target, precision oncology, biomarker, target profiling, side-effects, multi-target drug design.
Current Pharmaceutical Design
Title:Polypharmacology in Precision Oncology: Current Applications and Future Prospects
Volume: 22 Issue: 46
Author(s): Albert A. Antolin, Paul Workman, Jordi Mestres and Bissan Al-Lazikani
Affiliation:
Keywords: Polypharmacology, systems pharmacology, off-target, precision oncology, biomarker, target profiling, side-effects, multi-target drug design.
Abstract: Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single-target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients.
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Cite this article as:
Antolin A. Albert, Workman Paul, Mestres Jordi and Al-Lazikani Bissan, Polypharmacology in Precision Oncology: Current Applications and Future Prospects, Current Pharmaceutical Design 2016; 22 (46) . https://dx.doi.org/10.2174/1381612822666160923115828
DOI https://dx.doi.org/10.2174/1381612822666160923115828 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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